Neuroscience Learning and Memory Quiz

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Questions and Answers

What is the effect of inhibiting LTP during a learning experience?

It impairs memory of that experience. (correct)

It improves retrieval speed of the memory.

It has no effect on memory.

It enhances memory retention.

How do HPC-lesioned rats perform in the water maze task compared to normal rats?

They are incapable of locating the platform.

They find the platform more quickly.

They have increased latency in finding the platform. (correct)

They show no difference in latency.

What is the effect of AP5 (NMDAR antagonist) on water maze performance?

It decreases time taken to find the platform.

It completely blocks LTP induction. (correct)

It enhances platform location memory.

It has no effect on platform location memory.

In GLUA1 knockout mice, how does LTP at the CA3 -> CA1 synapse compare to their water maze performance?

LTP is impaired, but no water maze deficits are observed. Signup and view all the answers

What factor is primarily tested to assess spatial reference memory in rats during the water maze transfer test?

The quadrant in which they spend the most time. Signup and view all the answers

What is the term for the phenomenon where co-activation of separate inputs can induce long-term potentiation (LTP)?

Associativity Signup and view all the answers

Which condition must be met for a stimulation to induce LTP in a synapse according to the experimental evidence provided?

Stimulation above the cooperativity threshold Signup and view all the answers

What type of learning can LTP be considered a cellular analog of?

Associative learning Signup and view all the answers

What is the main role of NMDA receptors in the process of LTP?

To facilitate calcium influx needed for LTP Signup and view all the answers

What can long-term depression (LTD) be triggered by?

Repetitive low-frequency stimulation Signup and view all the answers

How does long-term depression (LTD) affect synaptic connections?

By erasing increases in EPSP size due to LTP Signup and view all the answers

Which of the following best describes the concept of cooperativity in relation to LTP?

Multiple inputs are necessary to produce a stronger response Signup and view all the answers

What is one effect associated with the increase in postsynaptic calcium concentration during LTP?

Activation of silent synapses Signup and view all the answers

Which process is primarily responsible for the maintenance of late-LTP?

Gene expression changes and protein synthesis Signup and view all the answers

What characterizes long-lasting LTP changes?

Increase in the number and size of synaptic contacts Signup and view all the answers

How does LTD primarily differ from LTP in terms of calcium levels?

Small slow increases in Ca2+ lead to LTD, while large fast increases lead to LTP Signup and view all the answers

Which mechanism is involved in the internalization during LTD?

Loss of AMPA receptors from the postsynaptic membrane Signup and view all the answers

Which statement is true regarding the effects of heterosynaptic changes?

They require coordinated activation of both synapses. Signup and view all the answers

What is the relationship between calcium concentration and synaptic strength during repetitive stimulation?

Increased presynaptic calcium concentration leads to potentiation lasting minutes. Signup and view all the answers

In terms of synaptic activation, what effect does facilitation primarily have?

Gradual decay over a few hundred milliseconds. Signup and view all the answers

What is a key factor influencing the electrical resistance in synaptic efficacy during synaptic changes?

Shortening of the spine necks Signup and view all the answers

Is there a definitive established connection between long-term synaptic changes and memory formation?

No, correlations exist but no definitive relationship has been established. Signup and view all the answers

What element's high permeability is crucial for the behavior of the NMDA receptor?

Ca2+ Signup and view all the answers

Which two conditions must be met for the NMDA receptor to open and allow LTP induction?

Glutamate binding and postsynaptic depolarization relieving Mg2+ block Signup and view all the answers

What characterizes the Early-LTP (E-LTP) phase in synaptic transmission?

It requires the activation of protein kinases but is independent of protein synthesis. Signup and view all the answers

What is the main role of increased Ca2+ in the postsynaptic cell during LTP induction?

It serves as a secondary messenger that initiates LTP. Signup and view all the answers

What prevents the opening of the NMDA receptor channel?

Magnesium block when at resting membrane potential Signup and view all the answers

Which phase of LTP involves lasting changes that can extend to years?

Late-LTP Signup and view all the answers

What is one potential mechanism by which LTP could manifest at the postsynaptic site?

Increase in number of AMPA receptors on the postsynaptic membrane Signup and view all the answers

What role does CaMKII play during LTP induction?

It activates signaling pathways triggered by Ca2+. Signup and view all the answers

What is the consequence of injecting Ca2+ chelators during the LTP process?

It blocks the induction of LTP. Signup and view all the answers

What is the role of detectability in establishing a memory according to the criteria mentioned?

It refers to observable changes in synaptic efficacy. Signup and view all the answers

Which criterion would be violated if LTP is prevented during a learning experience?

Detectability Signup and view all the answers

In the context of learning-induced LTP, what does retrograde alteration influence?

It modifies synaptic strength changes from past learning experiences. Signup and view all the answers

Which of the following statements accurately defines mimicry in the context of synaptic plasticity?

It enables the formation of false memories without real experiences. Signup and view all the answers

In Whitlock et al.'s (2006) study, how was memory measured in the inhibitory avoidance paradigm?

By observing the time taken for rats to enter the dark chamber. Signup and view all the answers

What key cellular markers indicated that LTP occurred after inhibitory avoidance training?

Enhanced GluR1 and GluR2 protein expression. Signup and view all the answers

What would likely happen if the synaptic weight changes from past learning experiences were altered?

It might lead to confusion regarding the learned behavior. Signup and view all the answers

Which experimental group served as a control in the inhibitory avoidance paradigm?

The group that was only exposed to the lighted chamber. Signup and view all the answers

What is the primary focus of the criteria discussed regarding memory formation?

The biochemical processes involved in learning and memory. Signup and view all the answers

How did the training in the inhibitory avoidance paradigm affect the phosphorylation of receptors?

It enhanced Ser831 phosphorylation as a marker for LTP. Signup and view all the answers

Study Notes

Synaptic Plasticity & Learning

Synaptic plasticity is activity-dependent changes in synaptic strength
Short-term plasticity: alterations lasting a few minutes or less, involving changes in synaptic transmission, varying in their time course and mechanisms; most altering transmitter release amounts
Long-term plasticity: alterations lasting 30 minutes or longer, including long-lasting strengthening or weakening of synaptic strength in mammalian brains (e.g., LTP, LTD), altering circuit function and potentially relating to learning and memory
Ongoing activity can result in short-term changes in synaptic efficacy via transmitter release

Synaptic Facilitation, Depression & Interaction

Synaptic facilitation: an enhanced response to a repeated stimulus, with subsequent responses increasing in magnitude
Synaptic depression: a weakening response to repeated stimulation, with subsequent responses decreasing in magnitude
Interaction involves both facilitation and depression, creating a net affect on synaptic responses

Post-Tetanic Potentiation (PTP)

PTP is stimulated by longer high-frequency trains of stimuli, which elicits synaptic depression, but a few seconds later elicits an increase in postsynaptic potential (PSP) amplitude.
PTP lasts for tens of minutes

Activity-Dependent Changes in Synaptic Efficacy

Long-term potentiation (LTP): a sustained enhancement of synaptic strength, dependent on activity; a long-lasting increasing synaptic strength
Long-term depression (LTD): a persistent reduction in synaptic strength, also activity-dependent; a long-lasting decrease in synaptic strength
Both LTP and LTD are broad terms referring to various diverse mechanisms

Trisynaptic Circuit: Dentate Gyrus

Defined, unidirectional information flow through the hippocampus, facilitating targeted stimulation to study synaptic function.
The circuit involves the dentate gyrus, CA3, and CA1 pyramidal cells, with inputs from the entorhinal cortex and outputs to other regions

Bliss & Lomo (1973)

Bliss and Lomo demonstrated that tetanic stimulation in the perforant path produced potentiated responses lasting hours (by increasing EPSP amplitude in the dentate granule cells).

Important Properties of LTP

Experience-dependent: LTP requires specific stimulation to produce a notable change in strength
Induced rapidly: a few seconds of stimulation can lead to lasting effects lasting hours
Cooperativity: a threshold intensity of stimulation is needed for the induction of LTP
Coincident activity: the coordinated activation of pre- and postsynaptic cells is necessary for LTP induction
Input Specificity: only activated pathways are potentiated
Associativity: simultaneous activation of separate but converging inputs produces LTP if occurring in a close temporal sequence

Experimental Evidence for 3 Properties of LTP

S2 stimulation alone is insufficient to induce LTP, falling below the cooperativity stimulus intensity threshold

Experimental Evidence for 3 Properties of LTP (input specificity)

SI stimulation is sufficient to induce LTP at the synapses stimulated, but not at others

Experimental Evidence for 3 Properties of LTP (associativity)

Simultaneous tetanus to both inputs allowed the weak input to benefit from the strong input

Coincident Activity

A single pulse to Schaffer collateral axons does not induce LTP on its own.
However, LTP is induced if the pulse is linked/paired with depolarization of the CA1 cell via a recording electrode

LTP as a Cellular Analog of Associative Learning

Before learning, a weak input (NS) is not potent enough, but the strong input (US) is sufficient.
During learning, the weak and strong inputs are sequentially paired, inducing a change in synaptic strength (LTP).
After learning, the weak input now elicits a response independently

How Long Can LTP Last?

The longest in-vivo experiment lasted up to 1 year.
The duration depends on the number of stimulation trains.
LTP can potentially serve as a mechanism for long-lasting information storage.

Long-Term Depression (LTD)

Repetitive low-frequency stimulation can reduce the size of postsynaptic potentials (EPSPs), inducing LTD.

Important Features of LTD

Similar to LTP, LTD can last for several hours and show input specificity.
It can be considered the opposite of LTP, reducing connections between brain regions or cells.
LTD can reverse LTP-induced EPSP increases.
It occurs through a complementary mechanism in synapses where LTP acts (by acting in the common synapse location)

Explaining LTP Features

This section discusses underlying mechanisms to understand LTP properties, such as cooperativity.

LTP Often Depends on Activation of NMDA Receptors

Drugs that block NMDA receptors impair LTP induction without affecting baseline responses.

The NMDA Receptor as a Coincidence Detector

The NMDA receptor channel opens only when glutamate is bound to the receptor and the postsynaptic cell is depolarized (relieving the Mg2+ block) simultaneously.

Different Mechanisms Underlying LTP Phases

Short-Term Potentiation (STP) (induction): minutes to 1 hour, NMDA receptor and postsynaptic Ca2+ dependent.
Early-LTP (E-LTP) (expression): 1-5 hours, protein kinase dependent (but not protein synthesis dependent).
Late-LTP (L-LTP) (maintenance): many hours to years, protein synthesis and RNA transcription dependent.

Increased Ca2+ in the Postsynaptic Cell

Increased intracellular calcium ([Ca2+]) in the postsynaptic cell triggers LTP induction.
This occurs through signal transduction cascades involving CaMKII and PKC.
Blocking Ca2+ chelators prevents LTP induction, accounting for the first hour of LTP.

How is LTP Actually Expressed?

Synaptic strengthening during LTP arises from an increase in the sensitivity of the postsynaptic cell to glutamate and requires at least 6 mechanisms, expressed on either the pre- or postsynaptic sides of the synapse

Activation of Silent Synapses

Activation of silent synapses is one major factor responsible for postsynaptic expression of early-LTP
Silent synapses (which initially lack AMPA receptors) become active by inserting AMPA receptors after LTP induction.

Late-LTP Depends on Gene Expression

Late-LTP involves changes in gene expression and synthesis of new proteins.
These proteins maintain the potentiation.

Long-Lasting LTP Changes

New dendritic spines can be observed as early as one hour after a stimulus.
Shortening/widening of spine necks reduces electrical resistance, increasing synaptic efficacy.

LTD Mechanisms

Similar to LTP, LTD requires NMDA receptor activation and Ca2+ entry for induction.
However, small and slow increases in Ca2+ lead to LTD, while rapid increases lead to LTP.
Activation of Ca2+-dependent phosphatases and loss (internalization) of AMPA receptors are integral to LTD.

Summary of Important Concepts (general overview)

Short periods of synaptic activation result in facilitation, depression, or augmentation of transmitter release.
Facilitation decays rapidly, while depression and augmentation persist.
Facilitation relates to increased cytoplasmic calcium concentration in the presynaptic terminal.
Longer periods induce post-tetanic potentiation (PTP) of transmitter release, mediated by presynaptic terminal calcium concentration increase
Repetitive stimulation can lead to activity-driven LTP or LTD in various CNS parts, with effects being homo- or heterosynaptic.
LTP enhances synaptic efficacy by increasing calcium concentration, inserting new receptors, and increasing receptor sensitivity in the postsynaptic cell.
LTD reduces efficacy by decreasing calcium concentration, potentially through decreasing or internalizing receptors

Summary of Important Concepts (LTP as a memory)

LTP is a measurable event in synaptic efficacy, a response to experiences.
Blocking LTP during learning impairs memory.
Altering synaptic weight changes that result from learning can alter memory.
Mimicking LTP can induce memory from past events that did not truly happen.

Does Learning Induce LTP?

Two-chambered box (light and dark): an experimental setup for learning where an animal learns to avoid the shock-associated side.
Inhibitory Avoidance Paradigm: animals learn to avoid the shock side based on the latency to enter
Control groups are essential to rule out alternative explanations.

Learning-Induced LTP

Whitlock et al. (2006) used the inhibitory avoidance paradigm to show that learning enhances phosphorylation and increases GluR1 and GluR2 protein levels, indicative of LTP induction.

Learning-Induced LTP (water maze)

In water maze studies, HPC-lesioned rats demonstrated an increased latency to find the escape platform. This indicates that the hippocampus is essential for spatial reference memory and performance.
Transfer tests assess location preferences (quadrant preference) when the platform is absent; indicating that animals still have spatial knowledge of the maze even without the cue of the platform.
LTP could be a neural mechanism underpinning learning.

Learning-Induced LTP (Cellular Markers)

Additional markers indicated LTP occurred after avoidance training including increases in GluR1 and GluR2 protein expression and phosphorylation of receptors

Inhibitory Avoidance Learning Induced LTP

Learning induces a fairly weak change in fEPSPs in CA1.
The weak change is clear to demonstrate a response in-vivo, but some effects in the population may be concealed due to an uneven sampling distribution.

Preventing LTP Before/During a Learning Experience

Preventing or blocking LTP during learning can impair learning and memory.

Water Maze (spatial reference memory)

Rats are trained to find a hidden platform in a water maze.
HPC-lesioned rats demonstrated an increased latency in finding the platform, indicating a hippocampal function for spatial reference memory.
Transfer tests measures location preference when the platform is absent.

Preventing LTP

Targeting NMDA receptors using AP5 blocks NMDA receptors, impacting downstream signaling and preventing LTP induction.
Blocking LTP induces problems in spatial learning and memory

Water Maze Performance with AP5

Intraventricular administration of AP5 (an NMDA receptor antagonist) blocks LTP induction in the hippocampus.
AP5 causes increased latency in finding the platform during training.
AP5 impairs the memory of platform location during transfer tests

Water Maze Performance in CaMKII Mutants

CaMKII knockout mice have impaired spatial tasks (in finding a visible platform), but this deficiency isn't directly due to hippocampal lesions.

Preventing LTP (methods)

Targeting NMDA receptors or disrupting downstream intracellular signaling involving CaMKII, and preventing AMPA receptor expression are methods for inhibiting LTP

Genetic Manipulation of AMPARs

Genetic manipulation of AMPA receptors (e.g., knockout of GluA1 subunit) impairs LTP in the CA3→CA1 synapses.

Spatial Reference Memory in CA1-NR1 KOs

Impairment of LTP is restricted to the CA1 region, where spatial reference memory is not affected (measured by behavioral tasks)

T-Maze (rewarded alternation)

A test of spatial working memory.
Complete and dorsal hippocampus lesions impair T-maze rewarded alternation performance.

T-Maze Alternation Performance with GluA1 KO Mice

GluA1 knockout mice exhibit T-maze alternation deficits but show normal water maze ability.
This highlights the specificity of AMPA receptors for certain types of memory.

Preventing LTP (summary)

Methods exist to target NMDA receptors to prevent LTP induction and Go-downstream to prevent intracellular signaling, including targeting CaMKII, and targeting AMPA receptors

CA1-Specific Genetic KO of NR1

NR1 knockout has a restricted effect specifically on the CA1 region.
The effect on the CA1 region is visible with impaired performance in a water maze task

Spatial Reference Memory in DG-NR1 KOS

Spatial reference memory is unaffected in DG-NR1 KOs. These mice are impaired in spatial working memory.

Hippocampal LTP

Hippocampal LTP isn't always a reliable measure of spatial learning and memory formation, as inhibiting it may not impair memory formation completely (some memories might have been created before interfering with LTP).

Is LTP Really a Memory Mechanism?

LTP may not fully account for all aspects of memory, as memories can persist even after LTP decays.
Research into alternative mechanisms of memory is ongoing.

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Test your understanding of long-term potentiation (LTP) and its role in learning and memory. This quiz explores the effects of NMDA receptors, spatial memory assessment in rats, and the differences in performance across various experimental conditions. Ideal for students of neuroscience and psychology.